This invention relates to oral products and methods of using same. More particularly, this invention relates to two-part oral products and methods of using same to remineralize subsurface lesions in teeth, mineralize exposed dentinal tubules, and prevent demineralization of the teeth.
Dental caries, i.e., tooth decay, is a leading cause of tooth damage in humans. Dental caries begins with lesions of so-called "white spots", which are demineralized areas below the surface of intact dental enamel. Subsurface lesions are formed before a cavity is detectable. If unchecked, surface enamel above a subsurface lesion eventually collapses, leading to cavitation and subsequent loss of tooth structure.
The primary component of the enamel and dentin in teeth is calcium phosphate in the form of calcium hydroxyapatite. Calcium hydroxyapatite is highly insoluble at normal oral pHs but relatively soluble in acidic media. Thus, carious lesions can form in the teeth when the teeth are exposed to acids, such as, e.g., those acids produced during the glycolysis of sugars by the action of various oral bacteria.
Saliva is supersaturated with respect to calcium and phosphate ions. Consequently, saliva can help protect the teeth against demineralization and can slowly remineralize teeth which have become demineralized. The presence of fluoride ions in the oral cavity can enhance the natural remineralization process, this being one of the accepted mechanisms by which fluoride toothpastes and mouthrinses protect against caries.
However, the efficacy of fluoride-containing toothpastes and mouthrinses to remineralize teeth is limited by the modest levels of calcium and phosphate in saliva.
Thus, it is highly desirable to increase the available concentration of calcium and phosphate ions in the oral cavity to speed up the remineralization process. However, because of calcium phosphate's low solubility at the pH of saliva, the addition of higher levels of dissolved calcium and phosphate ions is not easily accomplished.
Remineralization of dental enamel has been carried out experimentally, both in vivo and in vitro. Some studies have concentrated on the remineralizing properties of saliva and of synthetic solutions supersaturated with respect to hydroxyapatite. Such studies comprise the subject matter of U.S. Pat. Nos. 3,679,360 (Rubin) and 4,097,935 (Jarcho).
Generally, the supersaturated solutions or slurries used in the aforementioned Rubin and Jarcho patents for remineralization experiments have been prepared from a single form of calcium phosphate. When a carious lesion is flooded with one of these supersaturated solutions, the calcium and phosphate ions in the form of precipitated hydroxyapatite remineralize the lesion. However, use of these solutions is impractical for several reasons. First, the amount of calcium and phosphate ions available for remineralization in these supersaturated solutions is too low. It is reported that it takes approximately 10,000 unit volumes of the usual supersaturated solution to produce one unit volume of mineral. Thus, remineralization by this method requires both an excessive volume of fluid and an excessive number of applications. The supersaturated solutions are inherently limited in this respect because such solutions cannot maintain their supersaturated state. When the hydroxyapatite precipitates out to the point where the solution is no longer supersaturated, new supersaturated solution must be introduced or the remineralization process stops.
Thus, there is a need for a method of remineralizing dental enamel that does not require excessive amounts of solution or inordinately long or frequent exposure times.
Another problem with single calcium phosphate slurries is that as the hydroxyapatite precipitates out of solution, the pH of the solution changes. Unless the old solution is removed from contact with the tooth material, the solution may become too acidic or alkaline and may damage the dental tissue.
U.S. Pat. No. 4,080,440 (Digiulio et al) discloses a metastable solution of calcium and phosphate ions at a low pH (between 2.5 and 4.0) under which conditions the solubility of calcium phosphate salts is high. After penetration of the solution into demineralized enamel, remineralization results from the precipitation of calcium phosphate salts when the pH rises. Fluoride ions can be included in the metastable solution. A significant disadvantage of the use of metastable solutions is that the relatively low pH might demineralize the dental enamel and/or injure other tissue.
U.S. Pat. Nos. 4,177,258, 4,183,915 and 4,348,381 (Gaffar et al) disclose a remineralizing solution containing supersaturated concentrations of calcium ions, phosphate ions and a fluoride source stabilized by the presence of an antinucleating agent such as diamine tetramethylenephosphonic acid, ethylenediamine tetramethylenephosphonic acid and 2-phosphonobutane-tricarboxylic acid-1,2,4, or the water-soluble salts thereof. This solution is preferably adjusted to the neutral pH range where the solution is alleged to most effectively remineralize subsurface lesions. Even though the antinucleating agent would be expected to stabilize the solution, equilibrium of the supersaturated concentrations is still found difficult to maintain and avoid precipitation of hydroxyapatite and changes in the pH of the solution.
U.S. Pat. Nos. 4,083,955 (Grabenstetter et al) and 4,397,837 (Raaf et al) disclose a process for remineralizing demineralized enamel by the consecutive treatment of tooth surfaces with separate solutions containing calcium ions and phosphate ions. In this process, fluoride ions may be present in the phosphate solutions. It is immaterial which ionic solution is used to treat the teeth first. By sequentially applying calcium and phosphate ions to the tooth surface, high concentrations of the ions are able to penetrate into lesions in solution form, where the ions precipitate as a calcium phosphate salt when ions from the second treatment solution diffuse in. While apparently successful, this method involves the inconvenience of a plurality of sequential applications, which can also be time consuming.
U.S. Patent No. 4,606,912 (Rudy et al.) teaches a method of making a clear aqueous mouthwash solution capable of remineralizing lesions in teeth by forming an aqueous solution containing a source of calcium ions and a chelating agent for calcium ions, causing the chelation of at least 50% of the calcium ions and subsequently adding a source of phosphate ions to the aqueous solution. Here too, while somewhat effective, the addition and necessary control of the amount of chelating agent makes the concept impractical.
Another problem with known remineralization techniques is that the remineralization may stop before the lesion is completely remineralized due to build-up of the remineralized tooth material in or on the outer layer of the tooth's surface. This build-up occurs when the rate of remineralization is too fast and prevents the diffusion of the mineral into the deeper regions of the lesion, thus thwarting the full remineralization of the tooth.
U.S. Pat. Nos. 5,037,639; 5,268,167; 5,437,857; 5,427,768; and 5,460,803 (all to Tung) involve the use of amorphous calcium compounds such as amorphous calcium phosphate (ACP), amorphous calcium phosphate fluoride (ACPF) and amorphous calcium carbonate phosphate (ACCP) for use in remineralizing teeth. These amorphous compounds or solutions which form the amorphous compounds when applied either onto or into dental tissue prevent and/or repair dental weaknesses such as dental caries, exposed roots and dentin sensitivity. The compounds are claimed to have high solubilities, fast formation rates and fast conversion rates (to apatite).
In the methods taught in the Tung patents, remineralization is accomplished by bringing the amorphous compound into contact with the dental tissue. This can be done directly, i.e., putting an amorphous compound directly on the tooth, or indirectly through a carrier, i.e., incorporating the amorphous compound in a carrier such as a gel, a chewing gum, or a toothpaste and applying the carrier to the dental tissue. Once contact is established with the tooth, the amorphous calcium phosphate compounds will recrystallize to the less soluble apatite form in the lesion and reform the tooth. However, under conditions where amorphous calcium phosphate compounds are stable, the quantity of calcium and phosphate released is relatively low and, therefore, remineralization is slower than desirable.
The Tung patents also teach the use of two-part solutions wherein a first part contains phosphate salt(s) and a second part contains calcium salt(s), wherein either the first part or the second part further contains carbonate salt(s). In addition, the Tung patents teach solutions formed by dissolving in water a solid powder containing calcium salt(s), phosphate salt(s), and carbonate salt(s). These solutions are than applied to dental tissue. The Tung patents further teach the use of non-carbonated solid powders containing mixtures of calcium salts and phosphate salts which can be applied directly to the tooth or dispersed in gel, chewing gum, or other non-aqueous mediums such as toothpaste which is placed in contact with the tooth. The patents to Tung teach that these powders are easily dissolved in saliva and then reprecipitated as an amorphous calcium phosphate compound. However, the Tung patents do not disclose the pHs of aqueous solutions formed from the non-carbonated solid powder.
Effective remineralizing products and methods are continually desired which do not require the presence of carbonate salts to achieve stability, remineralization and/or mineralization. It is also continually desirable to provide remineralizing products and methods which directly form hydroxyapatite at the subsurface of the tooth rather than first forming an amorphous calcium phosphate as an intermediate.
Remineralizing products which overcome many of the aforementioned problems are disclosed in U.S. Patent Nos. 5,603,922 (Winston et al.); 5,605,675 (Usen et al.); 5,571,502 (Winston et al.); 5,614,175 (Winston et al.); and 5,645,853 (Winston et al.). Reference is also made to copending, commonly assigned U.S. patent application Ser. Nos. 08/669,724 (filed Jun. 26, 1996); 08/722,459 (filed Sep. 27, 1996); 08/670,897 (filed Jun. 26, 1996); 08/722,457 (filed Sept. 27, 1996); 08/691,328 (filed Aug. 2, 1996); and 08/832,827 (filed Apr. 3, 1997).
U.S. Pat. No. 5,603,922 (Winston et al.) discloses one-part and two-part products and methods of using same to remineralize subsurface lesions, wherein the products contain at least one water-soluble calcium salt, at least one water-soluble salt of a divalent metal other than calcium and at least one water-soluble phosphate salt. In the two-part products, the calcium and divalent metal salts are disposed in a first discrete component, and the phosphate salt(s) is disposed in a second discrete component. The two-part product may further contain a dispensing means for simultaneously dispensing the first and second components from the product so as to permit the dispensed first and second components to simultaneously contact the tooth or teeth being treated.
U.S. Patent No. 5,605,675 (Usen et al.) discloses a two-part product and method of using same for remineralizing dental enamel, wherein the product contains a first discrete component containing at least one water-soluble calcium salt and a second discrete component containing at least one water-soluble phosphate salt and at least one water-soluble fluoride salt. The product may further contain a means for simultaneously dispensing the first and second components from the product.
U.S. Pat. No. 5,645,853 (Winston et al.) discloses a chewing gum product and method of using same to remineralize subsurface lesions in teeth, wherein the product contains a water-soluble cationic portion composed of at least one water-soluble calcium salt and at least one water-soluble, non-toxic salt of a divalent metal other than calcium; a water-soluble anionic portion containing at least one water-soluble phosphate salt; and a gum base. The anionic and cationic portions are disposed in the product such that chewing of the product in the presence of water and/or saliva causes the anionic and cationic portions to be simultaneously released into the water and/or saliva so as to form a mixed aqueous solution therewith.
U.S. Pat. Nos. 5,571,502 and 5,614,175 (both to Winston et al.) each disclose one-part, non-aqueous products and methods of using same for remineralizing subsurface lesions, wherein the products contain at least one water-soluble calcium salt; at least one water-soluble phosphate salt; either a stabilizer or a hydrophilic, non-aqueous, water-soluble vehicle; and, optionally, at least one water-soluble fluoride salt. In the two-part products disclosed in the foregoing patents, separation of the cationic and anionic components is generally achieved by disposing the components in separate compartments of a two-compartment container. Although separation in this way is effective in preventing premature reaction of the cationic and anionic components, it is continually desirable to provide other ways to achieve separation of these components.
A primary object of this invention is to provide a two-part oral product capable of remineralizing subsurface lesions in teeth, mineralizing exposed dentinal tubules, and preventing demineralization of the teeth.
A further object of this invention is to provide a remineralizing, two-part oral product containing a discrete calcium part and a discrete phosphate part, wherein the calcium and phosphate parts are separated from one another by means other than a physical barrier therebetween.
Another object of this invention is to provide a remineralizing, two-part oral product the use of which does not require excessive amounts of solution or inordinately long or frequent exposure times.
Still another object of the present invention is to provide a remineralizing, two-part oral product which is easily usable by the consumer and does not differ significantly, in flavor or appearance, from customary dental cosmetics.
A further object of the present invention is to provide a method of remineralizing subsurface lesions, mineralizing exposed dentinal tubules and preventing demineralization of teeth, using a two-part oral product having the aforementioned characteristics.
These and other objects which are achieved according to the present invention can be readily discerned from the following description.